This proposal is concerned with the determinants of central apnea during sleep and the effect of central apnea on upper airway patency. Three specific aims will be investigated: 1) the effects of sleep state instability on ventilatory motor output; 2) the determinants of upper airway narrowing during central apnea; 3) the contribution of gender to the predisposition for breathing instability. The questions raised in this proposal are of great public health significance given the prevalence of sleep-disordered breathing. Human subjects spanning the spectrum of susceptibility to upper airway closure will be studied durin natural sleep. Sleep state instability will be induced by auditory stimulation, transient hypoxia or brief upper airway occlusion to test whether arousa induces a hyperpnea followed by hypopnea. Pharyngeal airway will be visualized by a fiberoptic pharyngscope. The effect of central apnea on upper airway patency will be investigated by inducing central apnea during sleep combined with fiberoptic imaging of the upper airway. The possible contribution of the pharyngeal constrictors to upper airway narrowing will be investigated. The effect of gender will be investigated by investigating the after- effects of hyperventilation in males and females during sleep. We anticipate that males will display a more profound inhibition of ventilatory motor output than females.